Biomedical subjects

R Wölfel

Publications and source records attributed to R Wölfel.

31 records · Page 2Linked to original sources

PubMed1994

[Pre- and postoperative radiotherapy to prevent heterotopic ossification of the hip joint].

BACKGROUND: In-vivo experimental data indicate that both pre- and postoperative radiotherapy can prevent heterotopic ossification after hip surgery. This comparison was clinically tested in a randomized study. PATIENTS AND METHODS: From June 1992 to September 1993, 84 patients with high risk for the development of heterotopic ossification were randomized. The treatment concept consisted either of preoperative radiotherapy within four hours prior to surgery (arm A) or postoperative radiotherapy within 72 hours following hip surgery (arm B). Preoperative radiotherapy was given in one fraction of 7 Gy, while the postoperative radiotherapy was delivered in five fractions of each 3.5 Gy (total 17.5 Gy). All patient variables (age, sex, prior surgery) and predisposing risk factors were comparable in both treatment arms. For the radiological assessment of heterotopic ossification according to (Brooker-Score) X-rays of the pelvis or hip were evaluated which had been taken immediately pre- and postoperatively as well as at least six months following surgery and prophylactic irradiation. The functional hip status was evaluated pre- and postoperatively using the Harris-Score. Cases in which the Brooker- and/or Harris-Score worsened during the postoperative follow-up as compared to the pre- and immediate postoperative situations were considered as treatment failures. RESULTS: Of 44 patients with at least six months follow-up 41 (93%) experienced a successful prophylaxis. Two failures were observed in the preoperative and one in the postoperative group. The prophylactic efficacy was not influenced if the pre- or postoperative interval was longer than prescribed. All intra- and postoperative complications were comparable for both treatment groups. The mean interval to partial strain (50% body weight) of the operated hip was longer in the preoperative group (mean 19 +/- 27 days) as compared to the postoperative group (mean 8 +/- 13 days). With respect to full strain (100% body weight), the results were equal in both groups. The functional hip status decreased in two patients. Again the mean overall improvement in the postoperative group was larger (mean 42.7 +/- 17.1 points) as compared to the preoperative group (mean 34.3 +/- 13.7 points). CONCLUSIONS: Preoperative and postoperative radiotherapy have equal prophylactic efficacy to prevent heterotopic ossification following hip surgery. The main advantage of preoperative radiotherapy are the simple management of the patient, the reduction of possible complications associated with transport and positioning of the patient in the postoperative period as well as excellent acceptance of this treatment concept by patients, nurses and staff.

Aged↗

PubMed1993

Prevention of heterotopic ossification (HO) after total hip replacement: randomized high versus low dose radiotherapy.

In a prospectively randomized study 60 hips at high risk for heterotopic ossification (HO) received prophylactic radiotherapy (RT). Randomization was performed between a low dose (LD-RT) of 5 x 2 Gy (arm A: 32 patients) and a high dose (HD-RT) of either 10 x 2 Gy (arm B1; 8 patients) or 5 x 3.5 Gy (arm B2; 20 patients). Relevant patient and risk factors were equally distributed in both treatment arms. 4 (7%) patients developed treatment failures. A short delay of RT after postoperative day (POD) 4 was significantly correlated with failure (p < 0.001). The results suggest no difference in prophylactic efficacy between LD-RT and HD-RT treatment. 2/19 (11%) patients receiving additional diphosphonates and 2/18 (11%) on no medication failed RT treatment, but none on indomethacin did so. In conclusion, immediate postoperative RT has been shown to be an effective prophylactic treatment.

Adult↗

PubMed1993

Prophylactic radiation therapy for prevention of heterotopic ossification after hip arthroplasty: results in 141 high-risk hips.

In a 4 1/2-year, prospectively randomized study, 137 patients with 141 hips at high risk for heterotopic ossification (HO) received prophylactic radiation therapy (RT). Patients were randomly assigned to a low-dose regimen of five fractions of 2 Gy each (n = 73) or a high-dose regimen of either 10 fractions of 2 Gy each (n = 7) or five fractions of 3.5 Gy each (n = 61). Treatment failure was assessed by comparing immediately postoperative radiographs with radiographs obtained at least 6 months after hip surgery (Brooker grading score). Positive responses (ie, effective prophylaxis of HO) were seen in 129 (91.5%) hips. Treatment failures were observed in 12 (8.5%). Use of a nonsteroidal antiinflammatory drug (NSAID) lowered the failure rate in both RT groups. High RT dose with a short duration (< or = 9 days) and use of an NSAID was significantly (P = .009) correlated with treatment success. RT delivered within a few days after hip surgery is effective in preventing HO, even in high-risk patients, and provides an excellent alternative for patients with contraindications to long-term medication with either NSAIDs or corticosteroids.

Adult↗

PubMed1993

[Eight years experience with the "Erlangen Model" titanium prosthesis--results of cementless implantation of 250 hip prostheses].

Between March 13, 1984 and March 28, 1988, 233 patients (age range from 21 to 73 years) with osteoarthritis of one or both hips were treated with the uncemented hip replacement "Erlanger Modell" (Prof. H. Beck/P. Brehm Chirurgie-Mechanik GmbH). The cause of the osteoarthritis was variable. Hip replacement was carried out for the following conditions: rheumatoid arthritis including ankylosing spondylits (n = 29), aseptic necrosis of the femoral head including posttraumatic and idiopathic forms (n = 17), osteoarthritis of unknown origin (n = 111), osteoarthritis following dysplasia or subluxation of the hips (n = 56) and loosened cemented hip prostheses (n = 37). Full weight bearing was not permitted for 50 days postoperatively, but mobilization and isometric exercises began 2 days after operation and isotonic exercises are introduced later. Complications included fracture of the femoral shaft during operation (3.3%), fracture of the femoral shaft postoperative (1.6%), dislocation (0.8) and infection early after operation (0.4%) and aseptic loosening (3.7%). Our results of 233 patients (250 joints), ranging from 4 to 8 postoperative years giving an average of 5.3 years, are encouraging. Good results based on patients satisfaction were obtained in 95.2% (83.8% after revision) and poor results in 1.0% (2.7% after revision). 3.8% (13.5 after revision) judged their situation as unchanged. 93.3% of the patients can walk without hooked stick (53.3% after revision), 90.2% of the patients can walk more than 1000m (69.4% after revision).

Adult↗

PubMed1993

[Results of cementless implantation of 150 "Erlangen Model" hip prostheses of titanium alloy Ti Al5 Fe2.5].

Between March 17, 1984 and August 20, 1987, 142 patients with osteoarthritis of one or both hips were treated by joint replacement with the uncemented "Erlangen" hip prosthesis (Prof. H. Beck/P. Brehm Chirurgie-Mechanik GmbH). The causes of the osteoarthritis varied. Hip replacement was carried out for the following conditions: rheumatoid arthritis including ankylosing spondylitis, aseptic necrosis of the femoral head, including posttraumatic and idiopathic forms, osteoarthritis of unknown origin, osteoarthritis following dysplasia or subluxation of the hips, and loosened cemented hip prostheses (131 primary implantations and 19 revisions). Full weight-bearing was not permitted for 50 days postoperatively, but mobilization and isometric exercises were started 2 days after operation and isotonic exercises were introduced later. Complications included fracture of the femoral shaft during operation and aseptic loosening. Our results in the 142 patients (150 joints) at 32-65 months (average 44 months) after surgery are encouraging. Good results based on patient satisfaction were obtained in 92.7% (81.3% after revision) and poor results in 7.3% (18.7% after revision). Most (90.2%) of the patients can walk without a stick (50.0% after revision), and 90.2% of the patients can walk more than 1000 m (68.8% after revision).

Alloys↗

PubMed1992

Evidence for various tryptamines and related compounds acting as substrates of the platelet 5-hydroxytryptamine transporter.

The aim of the present study was to answer the question whether amines other than 5-hydroxytryptamine (5-HT) and tryptamine act as substrates of the platelet 5-HT transporter. To this end, a large number of tryptamines, 5-HT receptor agonists and phenethylamines (which had IC50 values for 3H-5-HT uptake inhibition of 145-24,500 nmol l-1) was examined in rabbit platelets in order to determine their ability to induce an outward transport of 3H-5-HT. Platelets (the MAO of which was blocked) from reserpine-pretreated animals were loaded with 3H-5-HT and then exposed for 5 min to various concentrations (ranging from 0.25 to 40 times the IC50) of each compound. The concentration-effect curves for the drug-induced increase in 3H-5-HT efflux served to determine values of Emax (maximum increase in efflux expressed in % of the 3H-5-HT content of cells) and EC50 (drug concentration producing Emax/2). For the 24 compounds studied here (which included the 5-HT uptake inhibitors imipramine, citalopram, fluoxetine and cocaine) a linear correlation between EC50 and IC50 (r = 0.975) and a mean ratio of EC50/IC50 of 2.4 was found. Most of the compounds +ADe.g., (+/-)8-hydroxy-2-(N,N-dipropylamino)tetralin, S(+)alpha-methyl-5-HT, 5-carboxamidotryptamine and 5-methoxytryptamine+BD gave rise to Emax values (15.8-32.5%) that exceeded that brought about by imipramine (6.6%), indicating that they act as substrates of the 5-HT transporter; the 3H-5-HT outward transport observed in response to these substances was abolished in the presence of imipramine.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

Effects of imipramine and some tryptamine derivatives on the efflux of 3H-5-hydroxytryptamine from rabbit platelets.

The efflux of 3H-5-hydroxytryptamine (3H-5-HT) from rabbit platelets (monoamine oxidase inhibited; pretreatment with reserpine) was measured in the absence and presence of various concentrations of imipramine or a number of tryptamine derivatives. The maximum efflux-accelerating effect (Emax) of 5-HT and some other tryptamines (e.g., N-methyl-5-HT, 5-methoxytryptamine) far exceeded that of imipramine, whereas the Emax for 2-methyl-5-HT did not. It is concluded that tryptamines that are more effective in releasing 3H-5-HT than imipramine have the property of being substrates of the 5-HT transporter.

Analysis of Variance↗

PubMed1989

Plasma 3,4-dihydroxyphenylglycol as a tool to assess the role of neuronal uptake in the anaesthetized rabbit.

(1.) The purpose of this study was to investigate the role of neuronal uptake in the appearance in plasma of the primary noradrenaline metabolite 3,4-dihydroxyphenylglycol (DOPEG). To this end, steady-state changes in mixed central-venous plasma concentrations of noradrenaline and DOPEG produced by noradrenaline infusions or by changes in sympathetic tone were determined in anaesthetized rabbits either under control conditions or after treatment with desipramine (2 mg kg-1). The steady-state kinetics of infused DOPEG were also evaluated. (2.) Infused DOPEG (2.9 nmol kg-1 min-1 i.v. for 75 min) reached steady-state concentrations in plasma within less than 30 min, disappeared from plasma with a half-life of 2.3 min and showed a total-body plasma clearance of 84.0 ml kg-1 min-1. (3.) Constant-rate infusions of noradrenaline (1.2-5.9 nmol kg-1 min-1 i.v. for 75 min) produced increases in plasma noradrenaline and DOPEG concentrations which were linearly related to the rate of noradrenaline infusion. Thus, the plasma clearance of infused noradrenaline (75.8 ml kg-1 min-1) as well as the increase in plasma DOPEG expressed in % of that in plasma noradrenaline (9.4%) was virtually independent of the noradrenaline infusion rate. (4.) Desipramine reduced the plasma clearance of infused noradrenaline by 35.4% and the increment in plasma DOPEG relative to that in plasma noradrenaline by 75.3%.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia↗

PubMed1989

Effects of N-ethylmaleimide on 5-hydroxytryptamine transport and sodium content in rabbit platelets.

1. The present study analysed the mechanism underlying the inhibitory action of N-ethylmaleimide (NEM) on the 5-hydroxytryptamine (5-HT) uptake by blood platelets. 2. Rabbit platelets suspended in protein-free buffer were first preincubated for 45 min in the absence and presence of NEM (20 to 160 microM) or ouabain (0.5-2.0 microM) and then either analysed for their Na+ and K+ content or incubated (15s) with various concentrations of [3H]-5-HT (0.13-4.03 microM) to determine Km and Vmax for 5-HT uptake. 3. Both NEM and ouabain produced concentration-dependent decreases in Vmax with IC50 values of 52 and 0.58 microM, respectively. Neither drug changed Km significantly. 4. Both NEM and ouabain increased the Na+ and decreased the K+ content of platelets in a concentration-dependent manner. 5. There was a linear correlation between Vmax (expressed in % of control) and the reciprocal cellular Na+ content, with the results for both drugs falling onto one and the same regression line (r = 0.992; n = 8). This regression showed that an increase in Na+ content by 69% sufficed to reduce Vmax by 50%. 6. At concentrations that reduced 5-HT uptake by about 60%, neither NEM nor ouabain altered the potency of imipramine for inhibition of 5-HT uptake. 7. Hence, NEM inhibits 5-HT transport by inhibiting the Na+/K+-ATPase and not by a direct interaction with the 5-HT carrier. The consequential increase in the intracellular Na+ concentration reduces the transmembrane Na+ gradient and, therefore, hinders 5-HT inward transport. This action of the drug does not affect the ability of the carrier to bind 5-HT or imipramine.

Animals↗

PubMed1988

On the 5-hydroxytryptamine transport across the plasma membrane of rabbit platelets and its inhibition by imipramine.

1. The carrier-mediated uptake of labelled 5-hydroxytryptamine (3H-5-HT) in rabbit platelets (defined as the difference between uptake observed in the absence and presence of 10 mumol l-1 imipramine) was studied after inhibition of monoamine oxidase and after a 1:13 dilution of the platelet-rich plasma (PRP) with Tris-containing buffer. 2. Irrespective of whether the rabbits were pretreated with reserpine or not, initial rates of 3H-5-HT uptake were maintained for at least 15 s. 3. Analysis of the saturation kinetics of 3H-5-HT uptake using Hill's equation yielded Km, Vmax and nH values of 130 nmol l-1, 116 pmol 10(8) platelets-1 min-1 and 1.40, respectively. Pretreatment of the animals with reserpine did not affect any of these kinetic parameters, but depleted more than 99% of the platelets' 5-HT stores. 4. The nH value remained greater than unity when the duration of incubation with 3H-5-HT was extended from 15 to 30 s and when the uptake of 3H-5-HT was inhibited by the presence of imipramine (10-40 nmol l-1). However, it was reduced to unity (with a consequential increase in Km) when 300 nmol l-1 ketanserin was present. This concentration of ketanserin did not affect 3H-5-HT uptake at substrate concentrations far below Km. 5. Imipramine inhibited 3H-5-HT uptake by increasing the Km for 3H-5-HT without changing Vmax. The Ki for this interaction was 18 nmol l-1.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1988

Total body, systemic and pulmonary clearance and fractional extraction of unlabelled and differently 3H-labelled noradrenaline in the anaesthetized rabbit.

1. Rabbits were anaesthetized with urethane/chloralose and infused intravenously with trace amounts of 3H-2,5,6-, 3H-7,8- or 3H-7-(-)noradrenaline either without or with unlabelled (-)noradrenaline being simultaneously infused (0.2 micrograms kg-1 min-1). To obtain clearance values and extraction ratios for the pulmonary, systemic and total circulation, steady-state concentrations of infused noradrenaline were determined in mixed central venous (Cv) and arterial (Ca) plasma. Heart rate and blood pressure were recorded via the carotid artery, and the dye dilution method was used to determine the cardiac output of plasma. 2. The simultaneous infusion of unlabelled noradrenaline, which increased plasma levels of noradrenaline by a factor of 5, had no significant effect on either heart rate, blood pressure or cardiac output (when determined at steady state of the noradrenaline infusion). 3. The simultaneous infusion of unlabelled noradrenaline did not affect the clearance values of any of the three type of 3H-noradrenaline. Moreover, the clearances of the various types of 3H-noradrenaline were virtually identical and agreed with that of unlabelled noradrenaline. However, the clearance of labelled and unlabelled noradrenaline from arterial plasma was 1.15 times higher than that from central venous plasma. This factor corresponded to the ratio of Cv/Ca and pointed towards net removal of noradrenaline from the pulmonary circulation. 4. The fractional pulmonary extractions [1-(Ca/Cv)] of the three types of 3H-noradrenaline did not differ from each other and were not affected by the simultaneous infusion of unlabelled noradrenaline.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia↗

PubMedDate not supplied

The role of extraneuronal amine transport systems for the removal of extracellular catecholamines in the rabbit.

As selective inhibitors of the extraneuronal monoamine uptake system (uptake2) suitable for in-vivo studies were not available, the question of whether uptake2 plays a definite role in vivo is largely unresolved. We attempted to resolve the question by using 1,1'-diisopropyl-2,4'-cyanine iodide (disprocynium24), a novel agent that blocks uptake2 in vitro with high potency. Anaesthetized rabbits were infused with 3H-labelled noradrenaline, adrenaline and dopamine, and catecholamine plasma clearances as well as rates of spillover of endogenous catecholamines into plasma were measured before and during treatment with either disprocynium24 or vehicle. Four groups of animals were studied: group I, no further treatment: group II, monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT) inhibited; group III, neuronal uptake (uptake1) inhibited; group IV, uptake1 as well as MAO and COMT inhibited. Disprocynium24 (270 nmol kg-1 i.v. followed by an i.v. infusion of 80 nmol kg-1 min-1) did not alter heart rate and mean arterial blood pressure, but increased cardiac output by 22% and decreased the total peripheral vascular resistance by 16% with no difference between groups. When compared with vehicle controls, catecholamine clearances (normalized for the cardiac output of plasma) were decreased and spillover rates increased in response to disprocynium24. Although there were statistically significant between-group differences in baseline clearances (which decreased in the order: group I > group II > group III > group IV), the drug-induced clearance reductions relative to vehicle controls were similar in groups I to IV and amounted to 29-38% for noradrenaline, 22-31% for adrenaline and 16-22% for dopamine. Hence, there was still a significant % reduction in catecholamine clearances even after the combined inhibition of MAO and COMT, and there was no increase in the % reduction of clearances after inhibition of uptake1. Noradrenaline spillover increased in response to disprocynium24 in all four groups by 1.6- to 1.9-fold, whereas a 1.5- to 2.0-fold increase in adrenaline and dopamine spillover was observed in groups II and IV only. The results indicate that disprocynium24 interferes with the removal of circulating catecholamines not only by inhibiting uptake2, but also by inhibiting related organic cation transporters. As disprocynium24 increased the spillover of endogenous catecholamines into plasma even after inhibition of MAO and COMT, organic cation transporters may also be involved in the removal of endogenous catecholamines before they enter the circulation.

Adrenergic Agonists↗

PubMedDate not supplied

Enhancement of fatty acid mobilization and oxidation by glucose-xylitol compared to glucose alone in posttraumatic and septic patients.

INTRODUCTION: The objective of this study was to provide further information about the influence of xylitol on glucose and fatty acid metabolism after trauma and during sepsis. METHODS: In study I 18 metabolically normal patients undergoing coronary artery bypass grafting operation were randomly assigned into three groups. Group I (C I, n = 6) received 2 mg/kgBW/min of glucose, group II (C II, n = 6) 2 mg/kgBW/min of a glucose/xylitol mixture (1:1) and group III (C III, n = 6) 1 ml/kgBW/min of an isotonic saline solution. Infusions were applied over a 24-h-period following operation. Concentrations of glucose, lactate, insulin and single free fatty acids were measured before and after surgery and at 6-h-intervals over 36 hours postoperatively. In study II 5 septic patients were intravenously given 4 mg/kgBW/min glucose over a 6-h-period. Energy supply was then changed to a glucose/xylitol (1:1) regimen in an equicaloric dosage of 4 mg/kgBW/min for six hours again. Hepatic glucose production ([6,6-d2]-glucose), palmitate oxidation ([1-13C]-palmitate) and lactate concentrations were analyzed at the end of each infusion regime with the help of stable isotope technique and an enzymatic test, respectively. RESULTS: In study I glucose and insulin concentrations in C II and III were significantly lower than in C I during the postoperative infusion period. Highest lactate concentrations were measured in C I after 6 hours of infusion. Free fatty acids in C I remained at significantly lower levels compared to C II and III until glucose infusion was stopped. In septic patients (study II) xylitol led to significant lower hepatic glucose production rates and lactate concentrations than glucose, whereas palmitate oxidation increased. CONCLUSIONS: During the acute phase after trauma and during sepsis a carbohydrate supplementation with xylitol was superior to glucose alone because high plasma glucose concentrations were avoided, highly energy consuming hepatic glucose production was reduced and the release and oxidative utilization of free fatty acids was enhanced.

Blood Glucose↗